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血液系统恶性肿瘤中的泛素蛋白酶体系统:对其功能作用和治疗选择的新见解

The Ubiquitin Proteasome System in Hematological Malignancies: New Insight into Its Functional Role and Therapeutic Options.

作者信息

Di Costanzo Antonella, Del Gaudio Nunzio, Conte Lidio, Altucci Lucia

机构信息

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Vico L. De Crecchio 7, 80138 Naples, Italy.

Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), 20139 Milan, Italy.

出版信息

Cancers (Basel). 2020 Jul 14;12(7):1898. doi: 10.3390/cancers12071898.

Abstract

The ubiquitin proteasome system (UPS) is the main cellular degradation machinery designed for controlling turnover of critical proteins involved in cancer pathogenesis, including hematological malignancies. UPS plays a functional role in regulating turnover of key proteins involved in cell cycle arrest, apoptosis and terminal differentiation. When deregulated, it leads to several disorders, including cancer. Several studies indicate that, in some subtypes of human hematological neoplasms such as multiple myeloma and Burkitt's lymphoma, abnormalities in the UPS made it an attractive therapeutic target due to pro-cancer activity. In this review, we discuss the aberrant role of UPS evaluating its impact in hematological malignancies. Finally, we also review the most promising therapeutic approaches to target UPS as powerful strategies to improve treatment of blood cancers.

摘要

泛素蛋白酶体系统(UPS)是主要的细胞降解机制,旨在控制参与癌症发病机制的关键蛋白的周转,包括血液系统恶性肿瘤。UPS在调节参与细胞周期停滞、凋亡和终末分化的关键蛋白的周转中发挥功能作用。当失调时,它会导致包括癌症在内的多种疾病。多项研究表明,在人类血液系统肿瘤的某些亚型中,如多发性骨髓瘤和伯基特淋巴瘤,UPS的异常因其促癌活性而使其成为一个有吸引力的治疗靶点。在本综述中,我们讨论UPS的异常作用,评估其在血液系统恶性肿瘤中的影响。最后,我们还综述了针对UPS的最有前景的治疗方法,作为改善血液癌症治疗的有力策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44fd/7409207/a4f9a6c192b2/cancers-12-01898-g001.jpg

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